Prognostic Significance of P53 Mutation and Lymphovascular Space Invasion in Early-Stage and Locally Advanced Endometrioid-Type Endometrial Carcinoma

Objective: This study retrospectively analyzed patients diagnosed with early-stage and locally advanced endometrioid-type endometrial cancer. The primary objective was to evaluate the prognostic impact of p53 mutation status and lymphovascular space invasion (LVSI) on disease outcome, with a particular focus on overall survival (OS) and disease-free survival (DFS). Additionally, the study aimed to explore potential associations between p53 mutation status, LVSI, tumor stage, and histological grade. Method: Medical records of patients diagnosed with early-stage and locally advanced endometrioid-type endometrial cancer, who underwent surgery at the Gynecologic Oncology Department of Selçuk University Faculty of Medicine, had their pathological specimens examined by the Department of Pathology, and were subsequently followed in the Medical Oncology Department, were retrospectively reviewed. The prognostic impact of p53 mutation status and the presence of lymphovascular space invasion (LVSI) on disease-free survival (DFS) and overall survival (OS) was assessed. Data extracted from patient files included age at diagnosis, pathological diagnosis, date of diagnosis, date of surgery, disease stage according to the 2021 and 2023 FIGO staging systems, tumor grade, p53 mutation status, LVSI status, microsatellite instability (MSI) status, receipt of adjuvant chemotherapy and/or radiotherapy, presence of recurrence or metastasis, and date of death. Patients who underwent surgery between 2010 and 2023 were included in the study. Detailed evaluations of both p53 mutation status and LVSI were performed. The primary endpoint was the assessment of OS, while DFS was designated as the secondary endpoint. Results: The mean age of the 496 patients included was 58.4 ± 9.6 years. Among 495 patients with known p53 status, 89.7% were wild-type and 10.3% mutant-type. The distribution of p53 mutation across stages did not show a statistically significant difference (p = 0.052). LVSI was identified in 12.7% of all cases and showed a statistically significant increase with higher grade (8% in grade 1, 18% in grade 2, 36.8% in grade 3; p < 0.0001). In OS analysis, median OS was not reached for either p53 group; mean OS was 149.1 months for wild-type and 127.3 months for mutant-type, with no significant difference (p = 0.610). Similarly, median DFS was not reached; mean DFS was 142.5 months in wild-type and 113.0 months in mutant-type, with no significant difference (p = 0.100). LVSI presence significantly reduced OS (p < 0.0001): median OS was not reached in LVSI-negative patients but was 142.98 months in LVSI-positive patients; mean OS was 152.5 months vs. 109.4 months, respectively. In DFS analysis, the median was not reached for LVSI-negative patients, while LVSI-positive patients had a median DFS of 142.98 months and mean DFS of 98.8 months (p < 0.0001). Subgroup analysis by grade showed a significant impact of LVSI on mean OS (p = 0.003), with mean OS decreasing from 154.2 months (LVSI-negative) to 119.2 months (LVSI-positive) in grade 1, with similar significant reductions in grades 2 and 3. By stage, LVSI-positive patients in stage 2 had significantly shorter mean OS. In multivariate Cox regression analysis, LVSI was identified as an independent and significant prognostic factor for reduced OS (HR = 0.503; 95% CI: 0.289–0.875; p = 0.015). In contrast, p53 mutation status was not an independent prognostic factor in multivariate analysis. Conclusion: In early-stage endometrioid endometrial cancer, the presence of LVSI emerged as an adverse prognostic factor for both OS and DFS. The increasing frequency of LVSI with higher grade suggests a relationship with more aggressive tumor biology. p53 mutation status was not found to be an independent prognostic marker for survival in this study. These findings support considering LVSI as an important parameter in risk stratification and treatment planning.